Benzothiazole Carboxylate Diester Bifunctional Chelators for 64Cu PET Imaging in Alzheimer’s Disease

Herein we report a new series of bifunctional chelators (BFCs) with high affinity for amyloid β aggregates, strong binding affinity towards Cu(II), and favorable lipophilicity for potential blood-brain barrier (BBB) penetration. The alkyl carboxylate ester pendant arms enable high binding affinity towards Cu(II). The BFCs form stable ⁶⁴Cu-radiolabeled complexes and exhibit favorable partition coefficient (log D) values of 0.75-0.95. Among the five compounds tested, the ⁶⁴Cu-YW-1 and ⁶⁴Cu-YW-13 complexes exhibit significant staining of amyloid plaques in ex vivo autoradiography studies.